CD137 Identifies and Enriches for Tumor-Reactive T Cells


Get Permission

In a study reported in Clinical Cancer Research, Ye and colleagues showed that CD137 can be used to identify tumor-reactive T cells and to enrich for tumor-infiltrating lymphocytes and tumor-associated lymphocytes for use in adoptive immunotherapy.

In the study, tumor-infiltrating lymphocytes from resected ovarian cancer or melanoma were measured for surface CD137 expression directly or after incubation with tumor cells and cytokines. CD137-positive tumor-infiltrating lymphocytes were sorted and evaluated for antitumor activity.

In ovarian cancer studies, fresh tumor-infiltrating lymphocytes and tumor-associated lymphocytes expressed higher levels of CD137 vs circulating T cells. There was an HLA-dependent increase in CD137 expression after incubation of enzyme-digested tumor or ascites in interleukin [IL]-7 and IL-15 but not IL-2. Autologous tumor reactivity in vitro and in vivo was observed with enriched CD137-positive tumor-infiltrating lymphocytes, but not with PD-1–positive or PD-1–negative CD137-negative cells.

In melanoma studies, CD137 expression was increased in MART-1-specific CD8-positive tumor-infiltrating lymphocytes after incubation with HLA-matched MART-expressing cancer cells, with antigen-specific effector function being restricted to CD137-positive cells. CD137-positive cells induced greater antitumor effects in vivo compared with CD137-negative cells.

The investigators concluded, “Our findings reveal a role for the [tumor necrosis factor receptor]-family member CD137 in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of [tumor-infiltrating lymphocytes], thus rationalizing its agonistic engagement in vivo and its use in tumor-infiltrating lymphocyte selection for adoptive immunotherapy trials.” ■

Ye Q, et al: Clin Cancer Res 20:44-55, 2014.


Advertisement

Advertisement



;
Advertisement

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.